Studies of the effects of inhibiting histamine synthesis offer great promise but are hampered by the lack of effective and selective in vivo inhibitors of histidine decarboxylase. Present inhibitors block catabolism of histamine as well and probably inhibit many other enzyme systems that utilize pyridoxal as a cofactor. Recent pharmacological studies suggest a duality in the actions of histamine. This duality has been related to conformational aspects of the histamine molecule as calculated by quantum mechanical methods. Such calculations offer some insight into stereoelectronic characteristics of histamine receptors. Similar characteristics may be assumed for the active site of histidine decarboxylase. Based on this assumption, the purpose of this research is to develop potent, specific in vivo inhibitors of histamine synthesis and to gain further insight into the nature of the active site of histidine decarboxylase and its interaction with histidine in terms of the bound conformation of the latter. The ultimate objective of this research, in addition to providing tools for future studies of histamine physiology, is to provide more effective agents for antihistaminic therapy--agents that could block excessive histamine production at sites presumably not reached by conventional antihistaminic drugs.